Neuroprotective features of mesenchymal stem cells

Bone marrow (BM) derived mesenchymal stem cells (MSC) differentiate into cells of the mesodermal lineage but also, under certain experimental circumstances, into cells of the neuronal and glial lineage. Their therapeutic translation has been significantly boosted by the demonstration that MSC display significant also anti-proliferative, anti-inflammatory and anti-apoptotic features. These properties have been exploited in the effective treatment of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis where the inhibition of the autoimmune response resulted in a significant neuroprotection. A significant rescue of neural cells has been achieved also when MSC were administered in experimental brain ischemia and in animals undergoing brain or spinal cord injury. In these experimental conditions BM-MSC therapeutic effects are likely to depend on paracrine mechanisms mediated by the release of growth factors, anti-apoptotic molecules and anti-inflammatory cytokines creating a favorable environment for the regeneration of neurons, remyelination and improvement of cerebral flow. For potential clinical application BM-MSC offer significant practical advantages over other types of stem cells since they can be obtained from the adult BM and can be easily cultured and expanded in vitro under GMP conditions displaying a very low risk of malignant transformation. This review discusses the targets and mechanisms of BM-MSC mediated neuroprotection.

Introduction

Mesenchymal stem cells (MSC) were firstly identified by Friedenstein as stromal cells from the bone marrow (BM) and described as spindle-shaped cells in culture [1].

In this organ MSC represent a very rare population, less than 0,1% of nucleated cells representing progenitor cells of the stromal lineage at different stages of differentiation. They take part to the bone marrow microenviroment within the haematopoietic niche, supporting the mainteinance of hematopoietic stem cell (HSC) pool and the differentiation programs of blood born cells [2], *[3]. Beside their trophic role in the haematopoeitic niche, MSC are likely to play a similar role in other tissues where they display also an anti-proliferative activity resulting in tissue homeostasis [4]. In addition to adult bone marrow, MSC have been identified in several tissues and organs of either fetal or adult origin [5], [6], [7].

BM-derived MSC differentiate into fat, bone, and cartilage but can also transdifferentiate into embriological unrelated tissues [8]. They are easily cultured in vitro under appropriate conditions, grow as adherent cells until confluence resulting in yields sufficient for clinical exploitation for cell therapy or gene therapy strategies [9].